Id-1, a helix-loop helix protein, is a naturally occurring dominant negative inhibitor of helix-loop helix E proteins, which include E2A, E2-2 and HEB. Id-1 is expressed in progenitor lymphocytes and is downregulated during differentiation. Transgenic mice expressing Id-1 protein in either B or T cells arrest lymphocyte development. A pro-B cell specific enhancer was identified in the Id-1 gene and C/EBP transcription factors regulate its transcription. This renewal proposal will address two questions regarding the role of Id proteins in lymphocyte development. The first one is to address the mechanism underlying regulation of Id-1 gene expression and the consequences of the dysregulation of Id-1 in lymphocyte development. The second aim is to understand the molecular mechanism controlling Id-1 gene expression in B cells.